Purpose.The National
Institute of Allergy and Infectious Diseases (NIAID) invites new or renewal
applications from single institutions or consortia of institutions with
multi-disciplinary investigator teams to participate in the Centers for Medical
Countermeasures against Radiation (CMCR) program. The primary goal of this
Funding Opportunity Announcement (FOA) is to support development of new medical
products that will assess, diagnose, mitigate and/or treat the short- and
long-term consequences of radiation exposure after a radiological/nuclear
terrorist event. This research program originally established by NIAID in
fiscal year 2005 under RFA-AI-04-045 is now being reissued. All qualified
investigators are invited to apply; prior funding under this program or through
NIAID or NIH is not required.

Mechanism of Support. This FOA will
utilize the multi-project Cooperative Agreement (U19) mechanism.

Funds
Available and Anticipated Number of Awards. It is anticipated that approximately $24 million in
total costs will be available in FY 2010 to support this program and that 8-10
awards will be made. Awards issued under this FOA are contingent upon the
availability of funds and the submission of a sufficient number of meritorious
applications.

Budget and Project Period.The
total project period for an application submitted in response to this funding
opportunity may not exceed five years. Applicants may request no more than $3
million total costs per year.

Eligible Project Directors/Principal
Investigators (PDs/PIs). Individuals
with the skills, knowledge, and resources necessary to carry out the
proposed research are invited to work with their institution/organization
to develop an application for support. Individuals from underrepresented
racial and ethnic groups as well as individuals with disabilities are
always encouraged to apply for NIH support.

Number of
PDs/PIs. More than one PD/PI, or multiple PDs/PIs, may be
designated on the application.

Number of
Applications. Applicants may submit more
than one application provided that each application is scientifically
distinct.

The goal of the Centers for Medical Countermeasures against
Radiation (CMCR) program is to support basic, translational, and applied
research for the development of 1) new medical products to mitigate and/or
treat the acute and delayed effects of radiation exposure, as well as radiation
combined injury (radiation plus burns, wounds, trauma, or sepsis), and
radiation-induced multi-organ failure, and 2) improved radiation diagnostics, including high-throughput or
point-of-care radiation biodosimetry tools and predictive biomarker assays and
devices to assess early and/or delayed injury to different organs/tissues. Countermeasures should be aimed at having an impact on mitigation/treatment of
radiation injury to single and/or multiple organs with the ultimate goal of
restoring physiological function and improving survival and other relevant
clinical outcomes. NIAID envisions the development of a suite of medical
countermeasures and diagnostic tools for use in the management of radiation
casualties.

Background

Very few medical products
exist that have been shown to counter the acute and long-term injuries that can
result from a nuclear and radiological attack or accident. The threat of attack
has grown in recent years, with increased activity of global terrorist
organizations and a rise in illicit trafficking of radioactive
materials. The National Institute of Allergy and Infectious Diseases (NIAID),
National Institutes of Health (NIH) was given the responsibility by the
Department of Health and Human Services (DHHS) to identify, characterize and
develop new medical countermeasure products against radiological and nuclear
attacks that may cause a public health emergency.

In 2005, the NIH published
a Strategic Plan and Research Agenda for Medical Countermeasures against
Radiological and Nuclear Threats (http://www3.niaid.nih.gov/about/overview/planningPriorities/RadNuc_StrategicPlan.pdf).
This agenda includes focused product development, including medical
countermeasures for mitigation and treatment of acute radiation syndromes
(ARS), as well as development of radionuclide decorporation agents, and
biodosimetry devices. Several NIAID-supported contract and grant programs (http://www3.niaid.nih.gov/research/topics/radnuc/default.htm)
have been established to expand the medical options available to mitigate
and/or treat radiation injury after any radiological/nuclear terrorist attacks
or accidents. The CMCR network forms one part of this overall program. This
research and development program has already begun to yield new diagnostic
tools and leading candidates of mitigators/therapeutic agents. Continued successful development of medical
countermeasures, mitigators and/or treatments, and biomarker assays and devices
with the ultimate goal of restoring physiological function and improving survival will fill an
important need for the Strategic National Stockpile (SNS).

Under normal conditions, the hematopoietic,
gastrointestinal, cardiovascular, and central nervous systems (not to mention
the skin) interact with each other to maintain physiological homeostasis. It is
clear from data obtained from prior radiological and nuclear accidents that
these homeostatic mechanisms may be severely disturbed due to the compromise
and progressive physiological failure of these interdependent organ systems,
potentially leading to multiple organ failure and mortality. The management of
radiation casualties with multi-organ dysfunction syndrome is extremely complex
and effective medical countermeasures are lacking. Therefore, there is an
urgent need to develop clinical tools and new treatment strategies to treat
multiple organ failure and restore physiological functions of critical organs
after exposure.

Predicting the
severity and specific manifestations of injury in irradiated individuals is
also complex. Radiation injury can take days or weeks to present clinical
manifestations, and some delayed radiation injuries (such as fibrosis) may not
manifest clinically for months or years. Moreover, individuals may differ in
their sensitivity to radiation for a variety of reasons, including age, body
size, immune status, and genetic background. Finally, the severity of
injury to individual organs and tissues varies with radiation dose rate, quality
of radiation (low versus high linear energy transfer, LET), the heterogeneity
of exposure (partial versus total body), the source of exposure (external
radiation versus internal contamination), and could conceivably be modulated by
such factors as the bystander effect and the host’s adaptive response to
prior radiation exposure. Unfortunately, existing biodosimetry techniques and
devices have limited, if any, ability to discriminate such variables and they
do not predict the severity of injury sustained by specific organs and
tissues. Diagnostics that take account of such variables would facilitate
the prompt organ- and tissue-directed medical treatment that might be provided
by future medical countermeasures. Therefore, in addition to radiation dose assessment
through biodosimetry tools and techniques, there is a critical unmet need to
develop radiation-exposure biomarkers and devices that will predict the early
and/or delayed damage to specific organs and tissues to facilitate precise and
timely medical intervention, reduce morbidity, and save lives.

Research Objectives and Scope

The NIAID invites
applications from single institutions or consortia of institutions to establish
Centers for Medical Countermeasures against Radiation (CMCR) program. The
overall goal of this program is the development and maintenance of a strong
infrastructure combined with the multidisciplinary research expertise and
development capacity to generate new medical products that will diagnose,
mitigate the effects of, and treat the short- and long-term consequences of
radiation exposure from terrorist attacks or accidental exposure. To realize
this goal, the CMCR program will support: (1) conduct of investigator-directed
basic, translational, or applied research; (2) core facilities that support the
research and development activities of an individual CMCR; and (3)
translational research capacity to test and validate radiation
countermeasures/diagnostics for regulatory approvals.

The CMCR program
will support broad areas of multi-disciplinary research ranging from
identification, characterization and validation of biomarkers of radiation
injury to different organs/tissues, to development of new medical products to
treat short-term and delayed radiation injuries, radiation combined with burn,
blast, blunt trauma, wound injuries and/or concomitant infection and
multi-organ dysfunction. The scenarios of concern range from the use of a
radiological dispersion device (RDD), with a relatively limited number of
casualties incurred, to the detonation of improvised nuclear devices and
explosions or leaks at nuclear power plants, where large numbers of casualties
might be anticipated. Diverse research and development approaches are
encouraged, but all projects must be focused on medical products to diagnose,
mitigate/treat human injury incurred by radiological or nuclear attack, and
must describe their feasibility for human use under emergency conditions.
Countermeasures should be aimed at having an impact on mitigation/treatment of
radiation injury to single and/or multiple organs with the ultimate goal of
restoring physiological function and improving survival and other relevant
clinical outcomes. Basic discovery or mechanistic research is allowed, but it
must be made clear in the application that the results will contribute to a
product or medical approach that is feasible for human use and available to be
stockpiled for use in emergency situations.

This FOA will
support only development of medical countermeasures that can be used to
mitigate/treat radiation injuries when administered after radiation exposure
occurs
and
will not support development of medical products (i.e. radioprotectants) that
must be administered prior to exposure. Within the CMCR program, current
candidate products with mitigation or treatment potential will be moved into
validation and licensing studies to facilitate their inclusion in the Strategic
National Stockpile (http://www.bt.cdc.gov/stockpile/index.asp).The program
will support applied research and studies to advance products through needed
developmental stages when proposed by applicants with these capabilities. In
addition, new candidate products will be developed through basic and
translational research. The overall program is designed for optimal research
flexibility, synergy, and efficiency with the goal of rapidly developing
effective countermeasures for clinical use.

Examples of
desired criteria for medical countermeasures include:

easy
to produce in large quantities with low level of impurity;

effective
when administered 24hr or more after radiation exposure;

safe
for use in persons representative of the U.S. civilian population (inclusive of
children, the elderly, pregnant women, and persons with other medical
conditions);

non-teratogenic
to fetus;

easy
to administer; and

safe
for use in unexposed individuals.

Priority for
subsequent product development will be given to products that show efficacy
when administered 24 hr or later after radiation exposure.

CMCR Program Components

Each CMCR application must include the two
components described below: Research Projects and Core Activities

1. Research Projects

A minimum of three Research Projects are required each led by a different Project Leader. It is
expected that there will be a high level of synergy among the Research Projects
and that each project will include hypothesis-driven and hypothesis-generating
research, and/or descriptive or applied translational research focused on
biomarker/biodosimetry and/or radiation medical countermeasure.

The CMCR program is milestone-based and
includes the flexibility to quickly redirect or replace research projects
during the funding period. Explicit, quantitative, yearly Milestones must be included in each project of the proposed CMCR. It is recognized that
Milestones may require revision and re-negotiation prior to award, and during
the course of the project period. These Milestones will be used by NIAID
program staff in assessing progress and recommending continued funding on an
annual basis. Funding beyond the first year will be contingent upon
satisfactory progress in meeting negotiated milestones.

Areas of research and development interest for
the CMCR program include, but are not limited to the following:

Products and
regimens that mitigate and/or treat radiation injury to different
physiological systems/organs with emphasis on broad activity, ease of
administration, and safety;

Minimally invasive
biodosimetry devices and techniques, and other automated biology-based,
high-throughput diagnostic systems to rapidly assess levels and types of
radiation exposure, and to assess early and/or
delayed organ/tissue damage after the event and during treatment and
recovery phase;

(7) Characterization
and validation of biomarkers of mutagenesis and carcinogenesis.

Although research
involving human subjects (“clinical research”) is encouraged within
this program where relevant, clinical trials beyond Phase I will not be
supported. Applications proposing clinical trials beyond Phase I will not be
reviewed. For the NIH definition of clinical research versus clinical
trials, please see the Part II, Human Subjects Research Supplement at: http://grants.nih.gov/grants/funding/phs398/phs398.html.

Applications proposing studies in the excluded
areas will be considered non-responsive and will not be reviewed.

Restriction on
decorporation projects:

As the primary goal of the CMCR
program is to identify and promote the development of medical countermeasures
that diagnose, mitigate and/or treat radiation-induced normal tissue injury,no more than one project per application may focus on decorporating
agents/approaches. The total budget for a decorporation project should be no
more than 33% of the non-core expenditures for the total application.
Applications exceeding these limits will be considered non-responsive and will
not be reviewed.

2. Core Activities

A. An Administrative Core is required and will be responsible for the overall organization, management, decision-making, and periodic evaluations within the individual Center; as well as data sharing, protection of intellectual property, and involvement of institutional resources. The PD/PI(s) of the application must serve as the Core Leader(s) of the Administrative Core.

This Administrative Core will: organize
communications, group meetings, and teleconferences; organize the presentation
and publication of data; allocate and re-allocate resources to meet program
goals; prioritize fiscal and other resources; be responsible for resource
sharing and transmission of information and reagents; manage the budget for
program-related travel (including travel for the annual meetings – see
below); and identify and resolve problems and unexpected outcomes. Consortia
applicants must document commitment by all participant institutions and must
explain the organizational management, communications, logistics and
capabilities. This Core is also expected to create
and implement administrative and leadership mechanisms that will foster
effective interactions among the CMCR investigators and institutions to ensure
a productive research effort.

In addition, the Administrative Core is
required to support:

An External Scientific Advisory Group (ESAG).
The ESAG will be formed after award, and will evaluate scientific progress and
provide advice to the individual Center on an annual basis. In order to
maintain the largest possible reviewer pool for this FOA, applicants should not propose specific potential members of the proposed ESAG in the application and
ESAG candidates should not be recruited or contacted prior to review and
award. However, for renewal applications, any current or former ESAG members should
be identified. The duties and responsibilities of the ESAG must be defined in
the application. The budget request for the Administrative Core should include
the costs for travel of the ESAG members to meet with CMCR personnel on an
annual basis, and any additional meeting costs. A member of the CMCR program
may not serve as an ESAG member for a different CMCR Center.

B. A Pilot Projects Core is required and will support small studies to generate preliminary data
for the development and submission of future research applications for support
from non-CMCR sources. A designated Core Leader is required for the Pilot
Projects Core. Use of this Core should attract investigators new to the field
of radiation medical countermeasure development. The annual total costs for the
entire Pilot Projects Core must not exceed $300,000. Each Pilot Project
supported by this Core will be of limited duration (up to two years) and of
limited budget (up to $75,000 direct costs/year/project). Applications must
include a plan that describes the process by which requests for Pilot Projects
will be equitably solicited, reviewed, selected, and monitored. The selected
Pilot projects should be submitted to NIAID Program and Grants Management for
approval before actual implementation. The application must include a
plan that delineates methods for tracking the success of the Pilot Projects
program. Indicators of success should include the number of Pilot
Projects that obtain subsequent independent funding, investigational new drug (IND) orinvestigational device exemption (IDE) filings, patent applications and publications that result
from the Pilot Projects and other relevant measures. Specific Pilot Projects
should not be described within the application; only the process planned for
support and management of the program is to be described.

All Pilot Projects funded by CMCR awardees must
focus on areas of research and development interest for the CMCR program
described above. However, the topics need not be related to other research
being conducted at the parent Center. Pilot Projects that support research by
investigators outside of the parent CMCR group are encouraged and CMCR awardees
will be especially encouraged to fund collaborations with other members of the
CMCR network. Pilot Projects may also support research within the parent
Center.

Activities not allowed within the Pilot Projects Core include equipment purchase
and phase II, III, and IV clinical trials (see above). In addition, support for
an investigator, or for a specific project, is not allowed beyond a total of two
years during the entire five year funding period. All pilot projects must be
completed by the end of five year award period.

C. Scientific Cores (optional) may be proposed. A Science Core must support at least two of the proposed research projects. A designated Core Leader is required for each proposed Scientific Core. The application must indicate the specific projects to be served by the Scientific Core. This section of the application should present a clear picture of the facilities, techniques, and skills that the core will provide and describe the role of the Scientific Core Leader and each of the key participants. The apportionment of dollars, or percentage of dollars, that will be required to support each component research project which will utilize each scientific core should also be presented. Such core facilities should provide services that are already available, do not need to be developed, and cannot be funded through other means for the purposes proposed. Scientific Cores must be well justified within the description of the proposed core and also within each relevant Research Project description. Scientific Cores may include clinical, statistical, technical (e.g., flow cytometry, proteomics), informatics, or other non-administrative activities that directly support the research program.

If appropriate to the particular CMCR,
repositories for cells, tissues, reagents, or large data sets may be funded as
Scientific Core activities. In this case, applications should include methods
to obtain, protect, and archive relevant clinical and/or family history
information. In addition, appropriate informatics capability should be provided
to track data and link to other data sets. A plan for the distribution of
samples, reagents, data, and other resources should be included and conform to
the NIH policies on data and resource sharing (see Section III.6. Other
Submission Requirements).

Applications proposing Scientific Cores should
explain why those Core resources are not otherwise available at the applicant
institution or through other grant mechanisms, for example NIH-funded centers
programs or clinical networks.

CMCR Steering Committee

A Steering Committee will be established and
will serve as the governing board of this collaborative research program making
all major scientific and budgetary recommendations; its actions and decisions
will be determined by majority vote. Voting membership will include one
PD/PI from each CMCR.

Steering Committee responsibilities are further
described under Section VI.2.A.3. Cooperative Agreement Terms and Conditions of
Award – “Collaborative Responsibilities.”

This
funding opportunity will use the NIH
multi-project Cooperative Agreement (U19) grant award mechanism.
The Project Director/Principal Investigator (PD/PI) will be solely
responsible for planning, directing, and executing the proposed project.

This funding opportunity will use a
cooperative agreement award mechanism. In the cooperative agreement
mechanism, the Project Director/Principal Investigator (PD/PI) retains the
primary responsibility and dominant role for planning, directing, and executing
the proposed project, with NIH staff being substantially involved as a partner
with the PD/PI, as described in Section
VI.2.Administrative Requirements, "Cooperative Agreement Terms and
Conditions of Award.”

At this time, NIAID has not determined whether this solicitation will be
continued beyond the present FOA.

2. Funds Available

The
estimated amount of funds available for support of 8-10awards as a result of this
announcement is $24 million total costs for fiscal year 2010. Future year amounts will depend on annual
appropriations. The total project
period for an application submitted in response to this funding opportunity may
not exceed 5 years.

Although the size of award may vary with the
scope of research proposed, applicants may request no more than $3 million
total costs per year. Funds may not be used for renovations or
alterations.

Because the nature and scope of the proposed research will vary
from application to application, it is anticipated that the size and duration
of each award will also vary. Although the financial plans of the NIAID provide
support for this program, awards pursuant to this funding opportunity are
contingent upon the availability of funds and the submission of a sufficient
number of meritorious applications.

Facilities and administrative costs
requested by consortium participants are not included in the direct cost
limitation, see NOT-OD-05-004.

The decision of whether to apply for a single PD/PI or multiple
PD/PI grant is the responsibility of the applicant organization and should be
determined by the scientific goals of the project. Applications for multiple
PD/PI grants will require additional information, as outlined in the
instructions below. When considering multiple PDs/PIs, please be aware that the
structure and governance of the PD/PI leadership team as well as the knowledge,
skills, and experience of the individual PDs/PIs will be factored into the
assessment of the overall scientific merit of the application. Multiple PDs/PIs
on a project share the authority and responsibility for leading and directing
the project, intellectually and logistically. Each PD/PI is responsible and
accountable to the grantee organization, or, as appropriate, to a collaborating
organization, for the proper conduct of the project or program, including the
submission of all required reports. For further information on multiple
PDs/PIs, please see http://grants.nih.gov/grants/multi_pi.

Note that multiple Project Leaders or Core
Leaders are not allowed for individual Research
Projects, the Pilot Project Core, or the Scientific Cores. The Core
Leader(s) of the Administrative Core will be the PD/PI(s) of the overall
application.

Number of Applications.Applicants may submit more than one
application, provided they are scientifically distinct. A PD/PI may serve as a
Project Leader or Core Leader in another multi-project application under this
FOA provided there is no scientific overlap with the application submitted by
the PD/PI.

Resubmissions. Resubmission
applications are not permitted in response to this FOA.

Applications
must be prepared using the most current PHS 398 research grant application
instructions and forms. Applications must have a D&B Data Universal
Numbering System (DUNS) number as the universal identifier when applying for
Federal grants or cooperative agreements. The D&B number can be obtained by
calling (866) 705-5711 or through the web site at http://www.dnb.com/us/. The D&B number
should be entered on line 11 of the face page of the PHS 398 form.

The exceptions
from the PHS398 instructions and detailed information on the application
structure and components are provided in Section IV.6. Other Submission
Requirements. All applicants must follow the specific instructions in that
section.

The title and number of this funding
opportunity must be typed in item (box) 2 only of the face page of the
application form and the YES box must be checked.

SPECIAL
INSTRUCTIONS

Applications
with Multiple PDs/PIs

When
multiple PD/PIs are proposed, use the Face Page-Continued page to provide items
3a – 3h for all PD/PIs. NIH requires one PD/PI be designated as the
“contact PD/PI” for all communications between the PD/PIs and the
agency. The contact PI will be responsible for assembling the application
materials outlined below, and for coordinating the progress report for the
project. The contact PD/PI must meet all eligibility requirements for PD/PI
status in the same way as other PD/PIs, but has no special roles or
responsibilities within the project team beyond those mentioned above. The
contact PD/PI may be changed during the project period. The contact PD/PI
should be listed in block 3 of Form Page 1 (the Face Page), with all additional
PD/PIs listed on Form Page 1-Continued. When inserting the name of the PD/PI in
the header of each application page, use the name of the “Contact PD/PI,
et. al.” The contact PD/PI must be from the applicant organization if
PD/PIs are from more than one institution.

All
individuals designated as PD/PI must be registered in the eRA Commons and must be assigned the PD/PI role in that system (other roles such as SO or IAR will
not give the PD/PI the appropriate access to the application records). Each
PD/PI must include their respective eRA Commons ID in the eRA Commons User Name field.

All
projects proposing Multiple PDs/PIs will be required to include a new section
describing the leadership plan approach for the proposed project.

Multiple
PD/PI Leadership Plan: For applications designating
multiple PDs/PIs, a new section of the research plan, entitled “Multiple
PD/PI Leadership Plan” must be included. A rationale for choosing a
multiple PD/PI approach should be described. The governance and organizational
structure of the leadership team and the research project should be described,
and should include communication plans, process for making decisions on scientific
direction, and procedures for resolving conflicts. The roles and
administrative, technical, and scientific responsibilities for the project or
program should be delineated for the PDs/PIs and other collaborators.

If
budget allocation is planned, the distribution of resources to specific
components of the project or the individual PDs/PIs should be delineated in the
Leadership Plan. In the event of an award, the requested allocations may be
reflected in a footnote on the Notice of Award.

Multiple PD/PI Applications Involving a Single
Institution

When all PDs/PIs are within a single
institution, follow the instructions for non-modular budget preparation.

Multiple PD/PI Applications Involving Multiple
Institutions

When multiple institutions are involved, one
institution must be designated as the prime institution and funding for the
other institution(s) must be requested via a subcontract to be administered by
the prime institution. When submitting a detailed budget, the prime institution
should submit its budget using the non-modular budget component. All other
institutions should have their individual budgets attached separately to the
non-modular budget component of the prime institution.

Prospective
applicants are asked to submit a letter of intent that includes the following
information:

Descriptive title of proposed research

Name, address, and telephone number of
the Principal Investigator

Names of other key personnel

Participating institutions

Number and title of this funding
opportunity

Although a letter of
intent is not required, is not binding, and does not enter into the review of a
subsequent application, the information that it contains allows IC staff to
estimate the potential review workload and plan the review.

Applications
must be prepared using the forms found in the PHS 398 instructions for
preparing a research grant application. Submit a signed, typewritten original
of the application, including the checklist, and three signed photocopies in one package to:

Applications
must be received on or before the application
receipt date described above (Section IV.3.A.). If an application is received after
that date, the application may be delayed in the review process or not
reviewed. Upon receipt, applications will be evaluated for completeness
by the CSR and for responsiveness by the NIAID. Incomplete and
non-responsive applications will not be reviewed.

The NIH will not
accept any application in response to this funding opportunity that is
essentially the same as one currently pending initial review, unless the
applicant withdraws the pending application. However, when a previously
unfunded application, originally submitted as an investigator-initiated
application, is to be submitted in response to a funding opportunity, it is to
be prepared as a NEW application. That is, the application for the funding
opportunity must not include an Introduction describing the changes and
improvements made, and the text must not be marked to indicate the changes from
the previous unfunded version of the application.

All NIH awards are subject to the terms and conditions, cost
principles, and other considerations described in the NIH Grants Policy Statement. The Grants Policy Statement can be found at http://grants.nih.gov/grants/policy/policy.htm.

Pre-award costs are allowable. A grantee may, at its
own risk and without NIH prior approval, incur obligations and expenditures to
cover costs up to 90 days before the beginning date of the initial budget
period of a new or renewal award if such costs: are necessary to conduct the
project, and would be allowable under the grant, if awarded, without NIH prior
approval. If specific expenditures would otherwise require prior approval, the
grantee must obtain NIH approval before incurring the cost. NIH prior approval
is required for any costs to be incurred more than 90 days before the beginning
date of the initial budget period of a new or renewal award.

The incurrence of pre-award costs in anticipation of
a competing or non-competing award imposes no obligation on NIH either to make
the award or to increase the amount of the approved budget if an award is made
for less than the amount anticipated and is inadequate to cover the pre-award
costs incurred. NIH expects the grantee to be fully aware that pre-award costs
result in borrowing against future support and that such borrowing must not
impair the grantee's ability to accomplish the project objectives in the
approved time frame or in any way adversely affect the conduct of the project.
See NIH Grants Policy Statement http://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm.

6. Other
Submission Requirements

Supplemental Instructions for the Preparation
of Multi-project Applications

The following section supplements the
instructions found in the PHS Form 398 for preparing multi-project grant
applications that will be submitted in paper format. Additional instructions
are required because the PHS Form 398 is designed primarily for individual,
free-standing research project grant (R01) applications, and has no specific
instructions for multi-project applications consisting of research projects
interrelated by a common theme.

The supplemental instructions for multi-project
applications are divided as follows:

General Instructions – address collaborative efforts among research
projects, the administrative and organizational structure, as well as the
overall facilities and environment, and the overall budget.

Specific Instructions for Individual Projects – describe modifications to PHS Form 398
instructions on selected items to address the collaborative or interactive role
of the project.

Specific Instructions for Core Units – Cores must provide services or resources to
support at least two projects. Instructions describe modifications to PHS Form
398 instructions on selected items to address the collaborative or interactive
role of the project.

A. General Instructions

All applications must be submitted on PHS Form
398. The multi-project grant application should be assembled and paginated
as one complete document.

Items 1 - 14: complete these items as
instructed. This should be the first page of the entire application and all
succeeding pages should be numbered consecutively.

When multiple PDs/PIs are proposed, use the
Face Page-Continued page to provide items 3a-3h for all PDs/PIs. The Contact PI
should be listed on block 3 of Form Page 1-Face Page, with additional PDs/PIs
listed on the Face Page-Continued. All PDs/PIs must be registered in the eRA Commons prior to the submission of the application.

2. Form Page 2

Using Form Page 2 of the PHS 398, provide a
succinct but accurate description (abstract) of the OVERALL multi-project
application addressing the major, common theme of the program. Do not exceed
the space provided.

List the performance sites where the research
will be conducted.

Under "Key Personnel", list the
PD/PI(s) of the multi-project application, followed by the Leaders of the
component projects and cores, other key personnel, and then other significant
contributors.

When multiple PDs/PIs are proposed, list the
Contact PI first and then all additional PDs/PIs in alphabetical order. Lastly,
list all Key Personnel, giving name and organization.

3. Form Page 3 -
Table of Contents

Do not use Form Page 3 of the PHS 398; a more
comprehensive table of contents is needed for a multi-project application.

Bearing in mind that the application will be
scientifically reviewed project by project and core by core, prepare a detailed
Table of Contents that will enable reviewers to readily locate specific
information pertinent to the overall application as well as to each component
project and core. A page reference should be included for the budget for each
project and each core. Further, each research project should be identified by
number (e.g., Project 1), title, and responsible Project Leader, and each Core
should be identified by letter (e.g., Core A), title, and responsible Core
Leader. The page location of a COMPOSITE BUDGET should be indicated in the
"Table of Contents."

4. Composite
Budget

Do not use Form Page 4 of the PHS 398.Instead,
using the suggested format presented below, prepare a composite budget for all
proposed years of support. Justification for budget elements should not be
presented here but in the individual budgets of the projects and cores.

SAMPLE: Consolidated Total Direct Cost
Budget for All Proposed Years of Support

Component

Year 1

Year 2

Year 3

Year 4

Year 5

All Years

Project 1.

125,000

130,000

135,200

140,608

146,232

677,040

Project 2.

125,000

130,000

135,200

140,608

146,232

677,040

Project 3.

100,000

104,000

108,160

112,486

116,985

541,631

Core A. Admin. Core.

50,000

52,000

54,080

56,243

58,493

270,816

Core B. Scientific

25,000

50,000

52,000

54,080

56,243

237,323

Totals

425,000

466,000

484,640

504,025

524,185

2,403,850

5. Form Page 5

Complete the Total Cost line entries for all
requested budget periods (years) and the Total Cost for Entire Period of
Support entry. Detailed budgets are required within the descriptions of each
project and core (see below).

6. Biographical
Sketch Format Page

Biographical sketches of all professional
personnel for all components should be placed at the end of the application
with the PD/PI(s) first, followed by those of other key personnel in
alphabetical order.

7. Resources
Format Page

Do not complete. Essential information is to be
presented in the individual research project and core sections of the
application.

8. Program
Overview (Research Objectives and Strategic Plan)

This narrative section summarizes the overall
research plan for the multi-project application and is limited to 25 pages. The
multi-project application should be viewed as a confederation of interrelated
Research Projects, each capable of standing on its own scientific merit, but
complementary to one another. The synergies to be achieved through the
establishment of multi-disciplinary teams and novel collaborations should be
fully described. The overview provides an introduction to the proposed
research, outlines the specific questions to be explored, describes the key
preliminary data supporting the experimental approach, and addresses the
synergy of the individual Research Projects, the processes and procedures that
will be developed and utilized to administer the program, and the impact on
biomarker/biodosimetry and/or medical countermeasures development to
mitigate/treat radiation injury. This is an important section for it provides
the group of investigators an opportunity to give conceptual wholeness to the
overall program by providing an overview of the general problem area and by
laying out a broad strategy for attacking the problem. As the strategy
develops, each Project and Core should be cited briefly as to its place in the
overall scheme. Summarize the special features in the environment and/or
resources that make this application strong or unique.

If the application is a renewal, this
section should also highlight past performance and the major accomplishments
from the prior funding period as described in PHS 398 Instructions. In
addition to discussing results from individual projects, describe the synergy
and collaborations that occurred within the Program. Other points to include
are: which institutions were part of the prior CMCR; the numbers and quality of
publications; any patents filed; researchers brought into the study of
radiation biology; and how the CMCR was managed. For individual research
projects and cores that will be continued, additional details should be
provided in the Progress Report section of the Research Plan within each
research project and core.

9. Leadership Plan for Multiple PDs/PIs

For
applications designating multiple PDs/PIs, a section entitled “Multiple
PD/PI Leadership Plan” must be included and is limited to three
pages. A rationale for choosing a multiple PD/PI approach should be
described. The governance and organizational structure of the leadership
team and the research project should be described, and should include
communication plans, process for making decisions on scientific direction, and
procedures for resolving conflicts. The roles and administrative,
technical, and scientific responsibilities for the project or program should be
delineated for the PDs/PIs and other collaborators including
responsibilities for human or live vertebrate animal subject studies as
appropriate.

10.Checklist

One Checklist, placed at the end of the
application, is to be submitted for the entire application.

11. Appendix

Refer to Section IV.6. Other
Submission Requirements and Information, for instructions on submitting
appendix materials as described below.

For each project or core in the multi-project application, 3
publications plus other approved material are allowed.

The Face Page of the PHS 398 Form should not
be used as a cover page for individual research projects within a
multi-project application. Instead, use the PHS 398 continuation page to create
a "Cover Page" containing selected data about each individual
project. This Cover Page will demarcate each individual project and should
contain the following information items (these are a subset of the information
provided on a PHS 398 Face Page):

Provide a Description (abstract) of the
research proposed in the project according to the instructions on Form Page 2
of the PHS 398. In addition, the abstract should contain a brief description of
how the project will contribute towards attainment of the multi-project program
objectives.

List the performance sites where the research
will be conducted.

Under "Key Personnel", list the
Project Leader, followed by other key project personnel, and then other
significant contributors.

3. Form Page 3

Prepare a Table of Contents for the
project using Form Page 3 of the PHS 398.

4. Budget Pages (PHS 398 Form Pages 4 and 5).

Prepare a detailed budget and
justification for the research project using Form Pages 4 and 5 of the PHS 398.

5. Biographical Sketches

Do not repeat the biographical sketches of
participating investigators since this information will be included at the end
of the overall application (and therefore will be referenced in the Overall
Table of Contents).

6. Resources Format Page

Provide information on resources available for
the project.

7. Research Plan (Items 2-5 cannot exceed 25
pages)

Follow PHS-398 instructions.

A Progress Report must be provided for Renewal
applications. Provide the beginning and ending dates for the period covered
since the project was last reviewed competitively. Summarize the previous
application’s specific aims and the importance of the findings. Provide a
succinct account of published and unpublished results, indicating progress
toward their achievement. Discuss any changes in the specific aims as a result
of budget reductions.

8. Proposed
Yearly Milestones

Within 2 pages maximum (these pages
do not count against the 25 page limit for sections 2-5 of the Research Plan),
describe specific, quantitative Milestones that should be achieved in
each year of the Project. These Milestones will
not be given scores by reviewers and should be not considered in providing an
overall impact/priority score for the application. Milestones are
subject to negotiation with the NIH Program Officer prior to award and during
the course of the project period.

9. Appendix: Do not create a separate appendix for an individual
project. All appendix material should be collated as one body of material as
described below.

The Face Page of the PHS 398 Form should not
be used as a cover page for cores within a multi-project application.
Instead, use the PHS 398 continuation page to create a "Cover Page"
containing selected data about each individual core. This Cover Page will
demarcate each core and should contain the following information items (these
are a subset of the information provided on a PHS 398 Face Page:

Core Letter and Core Title: (e.g., A.
Radiation Core)

Name of Core Leader: (e.g., Smith, Robert
A.)

Human Subjects (Yes or No)

If Yes, Exemption Number

(or)

IRB Approval Date (e.g., 10/13/2009, or
Pending)

(and)

Federal wide Assurance (FWA) number

Vertebrate Animals (Yes or No)

If Yes, IACUC Approval Date (e.g., 10/13/2009,
or Pending)

(and) Animal welfare assurance number

Proposed Period of Support

From: (mmddyy, e.g., 07/01/2010)

To: (mmddyy, e.g., 06/30/2015)

Costs Requested for Initial Budget Period

(e.g., Direct Costs: $50,000)

(e.g., Total Costs: $70,000)

Costs Requested for the Entire Budget Period

(e.g., Direct Costs: $212,323)

(e.g., Total Costs: $297,252)

Applicant Organization (full address)

The
following are specific instructions for sections of the PHS 398 application
form that are to be completed differently than usual. For all other items
in the core application, follow the usual PHS 398 instructions.

2. Form Page 2

Provide a Description (abstract) of the
core activities and services according to the instructions on Form Page 2 of
the PHS 398. In addition, the abstract should contain a brief description of
how the core services will contribute towards attainment of the multi-project
program objectives.

List the performance sites where the core
activities and services will be conducted.

Under "Key Personnel", list the Core
Leader, followed by other key core personnel, and then other significant
contributors.

3. Form Page 3

Prepare a Table of Contents for the core
using Form Page 3 of the PHS 398.

4. Budget Pages (PHS 398 Form Pages 4 and 5)

Prepare a detailed budget and justification for
the core using Form Pages 4 and 5 of the PHS 398.

5. Biographical
Sketches

Do not repeat the biographical sketches of
participating investigators since this information will be located at the end
of the overall application (and therefore will be referenced in the Overall
Table of Contents).

8. Appendix: Do
not create a separate appendix for an individual Core. All appendix material
should be collated as one body of material as described above.

Awardees must agree to the “Cooperative
Agreement Terms and Conditions of Award” in section VI.2.A. “Award
Administration Information”.

Research
Plan Page Limitations

SeeSection IV.2, Content and Form of Application Submission for
research plan page limitations associated with single project applications and
see text above for page limitations associated with multi-project applications.

Do not use the Appendix to circumvent the
page limitations of the Research Plan component. An application that does not
observe the required page limitations may be delayed in the review process. See
Section 3B, “Sending an Application to NIH” for sending appendix
material.

Resource Sharing Plan(s)

NIH considers the sharing of unique
research resources developed through NIH-sponsored research an important means
to enhance the value of, and advance research. When resources have been
developed with NIH funds and the associated research findings published or
provided to NIH, it is important that they be made readily available for
research purposes to qualified individuals within the scientific community. If the
final data/resources are not amenable to sharing, this must be explained in
Resource Sharing section of the application. See http://grants.nih.gov/grants/policy/data_sharing/data_sharing_faqs.htm.

(a) Data Sharing Plan: Regardless of the amount
requested, investigators are expected to include a brief 1-paragraph
description of how final research data will be shared, or explain why
data-sharing is not possible.Applicants are encouraged to discuss
data-sharing plans with their NIH program contact. See http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-032.html.

(b) Sharing Model Organisms: Regardless of the
amount requested, all applications where the development of model organisms is
anticipated are expectedto include a description of a specific
plan for sharing and distributing unique model organisms and related resources,
or state appropriate reasons why such sharing is restricted or not possible.
See NIH
Guide NOT-OD-04-042.

(c) Genome-Wide Association
Studies (GWAS): Regardless of the amount requested, applicants
seeking funding for a genome-wide association study are expected to
provide a plan for submission of GWAS data to the NIH-designatedGWAS
data repository, or provide an appropriate explanation why submission to the
repository is not possible. A genome-wide association study is defined as
any study of genetic variation across the entire genome that is designed to
identify genetic associations with observable traits (such as blood pressure or
weight) or the presence or absence of a disease or condition. For further
information see Policy for Sharing of Data Obtained in NIH Supported or
Conducted Genome-Wide Association Studies, NIH
Guide NOT-OD-07-088,
and http://grants.nih.gov/grants/gwas/.

Section
V. Application Review Information

1. Criteria

Only the review criteria described below will be considered in the review
process.

2. Review and
Selection Process

Applications that are complete and responsive to the FOA will be
evaluated for scientific and technical merit by an appropriate peer review
group convened by NIAID and in
accordance with the review criteria stated below.

As part of the initial merit review, all applications will:

Undergo a selection process in which
only those applications deemed to have the highest scientific merit,
generally the top half of applications under review, will be discussed and
assigned an impact/priority score.

Receive a written critique.

Receive a second level of review by
the National Advisory Allergy and
Infectious Diseases Council.

The following will be considered in making
funding decisions:

Scientific
and technical merit of the proposed project as determined by peer review

Availability
of funds

Relevance
of the proposed project to program priorities

The
mission of the NIH is to support science in pursuit of knowledge about the
biology and behavior of living systems and to apply that knowledge to extend
healthy life and reduce the burdens of illness and disability. As part of
this mission, applications submitted to the NIH for grants or cooperative
agreements to support biomedical and behavioral research are evaluated for
scientific and technical merit through the NIH peer review system.

A singlenumerical
impact/priority score will be assigned to the whole application after
consideration of all of the elements. The overall impact/priority score for the
application will be based primarily on the scientific merit of the individual
components, with additional consideration of the overall synergy of the
Research Projects, integration of all the components, the overall program
organization, and the capabilities of the associated personnel. The overall
impact/priority score will depend on the perceived ability of the proposed work
to develop medical countermeasures against radiological and nuclear threats to
the civilian population. The clarity and completeness of the
application’s combined components with regard to specific goals, proposed
feasibility, and progress towards stated goals are critical.

Overall
Impact. Reviewers
will provide an overall impact/priority score to reflect their assessment of
the likelihood for the project to exert a sustained, powerful influence on the
research field(s) involved, in consideration of the following five core review
criteria, and additional review criteria (as applicable for the project
proposed).

Core
Review Criteria. Reviewers will consider each of the five review
criteria below in the determination of scientific and technical merit, and give
a separate score for each. An application does not need to be strong in
all categories to be judged likely to have major scientific impact. For
example, a project that by its nature is not innovative may be essential to
advance a field.

Significance. Does the
project address an important problem or a critical barrier to progress in the
field? If the aims of the project are achieved, how will scientific
knowledge, technical capability, and/or clinical practice be improved?
How will successful completion of the aims change the concepts, methods,
technologies, treatments, services, or preventative interventions that drive
this field? What is the likelihood that the
results of the proposed studies will be translated into new approaches, medical
products and diagnostics for treatment of short- and long-term consequences of
radiation exposure?

Investigator(s). Are the
PD/PIs, collaborators, and other researchers well suited to the project?
If Early Stage Investigators or New Investigators, do they have appropriate
experience and training? If established, have they demonstrated an
ongoing record of accomplishments that have advanced their field(s)? If
the project is collaborative or multi-PD/PI, do the investigators have
complementary and integrated expertise; are their leadership approach,
governance and organizational structure appropriate for the project?

Innovation. Does
the application challenge and seek to shift current research or clinical
practice paradigms by utilizing novel theoretical concepts, approaches or
methodologies, instrumentation, or interventions? Are the concepts,
approaches or methodologies, instrumentation, or interventions novel to one
field of research or novel in a broad sense? Is a refinement,
improvement, or new application of theoretical concepts, approaches or
methodologies, instrumentation, or interventions proposed?

Approach. Are the
overall strategy, methodology, and analyses well-reasoned and appropriate to
accomplish the specific aims of the project? Are potential problems,
alternative strategies, and benchmarks for success presented? If
the project is in the early stages of development, will the strategy establish
feasibility and will particularly risky aspects be managed? Are there sufficient preliminary data to support the
proposed research/development projects? Are there clear paths to translating
findings from basic mechanistic research study to development of new medical
countermeasures for treatment of radiation injuries?

If the project involves clinical research, are the plans for 1) protection of
human subjects from research risks, and 2) inclusion of minorities and members
of both sexes/genders, as well as the inclusion of children, justified in terms
of the scientific goals and research strategy proposed?

Environment. Will the scientific environment in which the work will be
done contribute to the probability of success? Are the institutional
support, equipment and other physical resources available to the investigators
adequate for the project proposed? Will the project benefit from unique
features of the scientific environment, subject populations, or collaborative
arrangements?

Additional
Review Criteria for Multi-Project (U19) Applications Only

Administrative Core: Reviewers will consider each of the criteria below in the
determination of scientific and technical merit. Is the administrative and organizational structure
appropriate and sound to facilitate attainment of the objective(s) of the
proposed program? Is the management plan for fiscal accountability and
communications within the overall program appropriate? Are the plans for
coordination, problem identification and resolution, and the establishment of a
strong collaborative environment for the program appropriate? Is the
experience, level of commitment, and availability of the Administrative Core
Leader(s) and administrative staff adequate to manage the overall program? Are
the plans to utilize the External Scientific Advisory Group adequate?

Scientific Cores: Reviewers will consider each of the criteria below in the
determination of scientific and technical merit: Is provision of resources and core
services for the individual Research Projects critical and justified?Is
the relationship of a scientific core to the central focus of the overall
program strong?Is the quality of the relevant facilities or
services provided and criteria for prioritization and usage appropriate?Are the qualifications, competence, and commitment of the Core Leader and
key personnel appropriate?

Pilot Project Core: Reviewers will consider each of the criteria below in the
determination of scientific and technical merit: Is the
experience, level of commitment, and availability of the Pilot Projects Core
Leader and staff adequate to manage the pilot program? Are the plans for
solicitation, review, administration, evaluation, and fiscal accountability of
pilot funds appropriate and sound? Are there adequate plans to track outcomes
of Pilot Project support?

Overall Impact of the Multi-Project Application: The
following items will be considered in the determination of the overall
scientific and technical merit and impact/priority score for the entire
multi-project application. Are the adequacy and significance of the proposed
center’s plan to develop medical countermeasures that will mitigate/treat
radiation injuries and/or develop improved radiation diagnostics, such as
high-throughput and point-of-care radiation biodosimetry tools or predictive
biomarker assays and devices that assess early and/or delayed injury to
different organs/tissues well described and justified? Are the plans to
establish, coordinate, and manage a synergistic research program to achieve the
goals of the CMCR including plans for equitable resolution of conflicts and
decision-making adequate and justified? Is the scientific gain achieved by
combining the component Research Projects into a multi-project program beyond
that which is achievable if each project were to be pursued independently
(synergy) clearly described and justified? Is the overall program cohesive,
including coordination and interrelationships among individual components
focused on a common theme? Is there potential for productive collaboration
among scientists within the CMCR network? Does the PD/PI have the leadership
and scientific ability to develop an integrated, multi-disciplinary program
with a well-defined central research focus, and commitment and ability to
devote adequate time and effort to the program? For applications designating
multiple PDs/PIs, is the Leadership Plan appropriate and adequate to ensure
that there will be sufficient coordination and communication among the PDs/PIs?
For renewal applications, were there adequate accomplishments achieved during
the prior funding period? Are there significant
synergy and thematic relatedness between the projects?

2.A. Additional Review Criteria

In addition to the above
criteria, the following items will continue to be considered in the
determination of scientific merit and the impact/priority score:

Protections for Human Subjects. For
research that involves human subjects but does not involve one of the six
categories of research that are exempt under 45 CFR Part 46, the committee will
evaluate the justification for involvement of human subjects and the proposed
protections from research risk relating to their participation according to the
following five review criteria: 1) risk to subjects, 2) adequacy of protection
against risks, 3) potential benefits to the subjects and others, 4) importance
of the knowledge to be gained, and 5) data and safety monitoring for clinical
trials.

For research that involves human subjects and meets
the criteria for one or more of the six categories of research that are exempt
under 45 CFR Part 46, the committee will evaluate: 1) the justification for the
exemption, 2) human subjects involvement and characteristics, and 3) sources of
materials.

Inclusion of Women, Minorities, and Children.
When the proposed project involves clinical research, the committee will
evaluate the proposed plans for inclusion of minorities and members of both
genders, as well as the inclusion of children.

Vertebrate Animals. The
committee will evaluate the involvement of live vertebrate animals as part of
the scientific assessment according to the following five points: 1) proposed
use of the animals, and species, strains, ages, sex, and numbers to be used; 2)
justifications for the use of animals and for the appropriateness of the
species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for
limiting discomfort, distress, pain and injury to that which is unavoidable in
the conduct of scientifically sound research including the use of analgesic,
anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and
5) methods of euthanasia and reason for selection if not consistent with the
AVMA Guidelines on Euthanasia.

Renewal Applications.
When reviewing a Renewal application (formerly called a competing continuation
application), the committee will consider the progress made in the last funding
period.

Biohazards. Reviewers will
assess whether materials or procedures proposed are potentially hazardous to
research personnel and/or the environment, and if needed, determine whether
adequate protection is proposed.

2.B. Additional Review
Considerations

As applicable for the project proposed,
reviewers will address each of the following items, but will not give scores
for these items and should not consider them in providing an overall impact/priority
score.

Budget and Period Support.
Reviewers will consider whether the budget and the requested period of support
are fully justified and reasonable in relation to the proposed research.

Milestones. Reviewers will comment
on the adequacy and appropriateness of the yearly Milestones for each of the
Research projects

Select Agent Research. Reviewers will assess the information provided in this section of the
application, including 1) the Select Agent(s) to be used in the proposed
research, 2) the registration status of all entities where Select Agent(s) will
be used, 3) the procedures that will be used to monitor possession use and
transfer of Select Agent(s), and 4) plans for appropriate biosafety,
biocontainment, and security of the Select Agent(s).

A formal
notification in the form of a Notice of Award (NoA) will be provided to
the applicant organization. The NoA signed by the grants management officer is
the authorizing document. Once all administrative and programmatic issues have
been resolved, the NoA will be generated via email notification from the
awarding component to the grantee business official.

Selection
of an application for award is not an authorization to begin performance. Any
costs incurred before receipt of the NoA are at the recipient's risk. These
costs may be reimbursed only to the extent considered allowable pre-award
costs. See Also Section IV.5. Funding Restrictions.

The following Terms and Conditions will be
incorporated into the award statement and will be provided to the Principal
Investigator as well as to the appropriate institutional official, at the time
of award.

2.A. Cooperative Agreement Terms
and Conditions of Award

The
following special terms of award are in addition to, and not in lieu of,
otherwise applicable OMB administrative guidelines, HHS grant administration
regulations at 45 CFR Parts 74 and 92 (Part 92 is applicable when State and
local Governments are eligible to apply), and other HHS, PHS, and NIH grant
administration policies.

The
administrative and funding instrument used for this program will be the
cooperative agreement an "assistance" mechanism (rather than an
"acquisition" mechanism), in which substantial NIH programmatic
involvement with the awardees is anticipated during the performance of the
activities. Under the cooperative agreement, the NIH purpose is to support and
stimulate the recipients' activities by involvement in and otherwise working
jointly with the award recipients in a partnership role; it is not to assume
direction, prime responsibility, or a dominant role in the activities.
Consistent with this concept, the dominant role and prime responsibility
resides with the awardees for the project as a whole, although specific tasks
and activities may be shared among the awardees and the NIH as defined below.

The PD/PI will have the primary responsibility for: defining the research plan and goals;
overseeing/performing the scientific activities of the plan; ensuring
successful completion of Milestones within the timeframe and budget proposed;
cooperating with NIAID programmatic, technical, and administrative staff; and
administratively managing the U19. One PD/PI from each CMCR will be a voting member
of the CMCR Steering Committee (see below), will participate in all Steering
Committee activities, and will follow the policies and procedures developed by
the Steering Committee. Awardees must be committed to making research samples
and tools, methods, data, and materials that they develop under this program
available to other members of this program as well as the research community,
subject to the rights described below.

All clinical activities performed under this
award must be in compliance with all U.S. Federal regulations, guidance, and
NIH policies applying to the conduct of research involving human subjects and
regulatory applications for new drug or biological licenses when applicable.
These include, but are not limited to: U.S. Code of Federal Regulations (CFR)
Title 21, Parts 11, 50, 54, 56, 312, 314, 601 and Title 45, Part 46; ICH
guidance for Good Clinical Practice (GCP); and NIH grants policy (refer to http://grants.nih.gov/archive/archive/grants/policy/nihgps_2003/index.htm).
In addition, the awardee must ensure that all sites in the U.S. and outside the U.S. comply with the following:

Each institution
engaged in human subjects research has a current, approved Assurance
Number on file with the DHHS Office for Human Research Protections
(OHRP).

For Investigational
New Drug (IND) studies, each local Investigator of Record has supplied a
completed FDA Form 1572 to NIAID for each protocol conducted at each site.
INDs may be held by the PD/PI, by a commercial subcontractor, or by the
NIAID.

Each study
investigator and sub-investigator has provided current curriculum vitae to
NIAID.

Each study
participant (or legal representative) will sign an IRB/EC-approved
protocol consent prior to entry on study as part of the Informed Consent
Process.

All clinical
research activities performed outside of the U.S. must, in addition to
U.S. Federal regulations, comply with the host country regulations for
human subjects.

Milestones

The applicants will describe explicit, quantitative,
yearly Milestones for each Research Project of the proposed CMCR. It is
recognized that Milestones may require revision and re-negotiation prior to
award and during the course of the project period. The NIH Program Official will
negotiate the Milestones with the PD/PI(s) and provide approvals. Release of
each yearly funding increment by NIAID will be based on a NIAID review of
progress towards achieving the previously agreed upon Milestones.

External Scientific Advisory Group

After award, the PD/PI will establish an
External Scientific Advisory Group (ESAG) comprised of three to four
investigators who are not a part of the overall CMCR program. The ESAG will
meet annually with the Center personnel to evaluate progress and provide advice
on future directions. Costs will be borne by the awardee.

Pilot Studies

The PD/PI will be responsible for ensuring that
all pilot studies involving human or animal subjects have the appropriate
clearances (i.e., IRB, FWA, IACUC, human subjects’ research training, and
other required documentation in domestic and foreign institutions) prior to
implementation. All pilot projects need to be approved by the NIAID Program and
Grants Management prior to initiation. The PD/PI must inform the NIH of any
awards made for pilot studies involving foreign sites prior to their
initiation. Pilot studies involving foreign sites cannot be initiated without
first obtaining NIH clearance and approvals for protection of human subjects
and animals, including specimens.

Site Visits

The PD/PI will host site visits by NIAID
program staff as requested by the program staff. These site visits may be held
in conjunction with meetings of the CMCR members with their ESAG.

Intellectual Property

The awardee is solely responsible for the
timely acquisition of all appropriate proprietary rights, including
intellectual property rights, and all materials needed for the applicant to
perform the project.

Before, during, and subsequent to the award,
the U.S. Government is not required to obtain for the awardee any proprietary
rights, including intellectual property rights, or any materials needed by the
awardee to perform the project.

The awardee is required to report to the U.S.
Government all inventions made in the performance of the project, as specified
by 35 U.S.C. Sect. 202 (Bayh-Dole Act).

Awardees are expected to make new information
and materials known to the research community in a timely manner through
publications, web announcements, and reports to the NIAID, or other mechanisms.

Publications

The PD/PI will be responsible for the timely submission of
all abstracts, manuscripts and reviews (co)authored by members of the grant and
supported in part or in total under this Agreement. The PD/PI and Project
Leaders are requested to submit manuscripts to the Program Officer within two
weeks of acceptance for publication so that an up-to-date summary of program
accomplishments can be maintained and joint press conferences and press
releases prepared. Publications or oral presentations of work performed under
this Agreement are the responsibility of the PD/PI and appropriate Project
Leaders and will require appropriate acknowledgement of NIAID support. Timely
publication of major findings is encouraged.

2. A.2. NIH Responsibilities

An NIH Project Scientist will have substantial programmatic
involvement that is above and beyond the normal stewardship role in awards, as
described below.

A program official from the NIAID Division of Allergy, Immunology, and
Transplantation (DAIT) will serve as the NIH Project Scientist for this
program. In conjunction with other NIAID scientific program staff and the CMCR
Steering Committee (see below), the NIH Project Scientist will provide advice
and guidance on technical issues, such as reviewing progress or recommending
changes. Administrative assistance will be provided by the NIH Project
Scientist in conjunction with the NIAID Grants Management Office. The NIH
Project Scientist may also: provide input into the design of activities;
advise in the selection of sources or resources (e.g., determining where a
particular reagent may be found); coordinate or participate in the collection
and/or analysis of data; or advice in the management and technical performance.

The NIH Project Scientist will schedule the meetings and teleconferences of the
Steering Committee, and ensure coordination of Steering Committee activities
and implementation of its recommendations, decisions, and policies.

Additionally, an agency Program Official or IC Program Director
will be responsible for the normal scientific and programmatic stewardship of
the award and will be named in the Notice of Grant Award. The assigned Program
Official may also serve as the Project Scientist.

2.A.3. Collaborative Responsibilities

CMCR Steering Committee

A Steering Committee will be established to
serve as the governing board of the CMCR program. The committee will be
comprised of PD/PI of each U19 grant and the NIAID Project Scientist, and may
also include other individuals with expertise in the scientific areas, as well
as Program Officials from the NIAID, National Cancer Institute, and other NIH
institutes as appropriate. Only one PD/PI from each U19 grant will be voting
members of the Steering Committee and each will have one vote. Awardees will be
required to accept and implement policies approved by the Steering Committee.

The CMCR Steering Committee will meet quarterly
by teleconference, except for one yearly face-to-face meeting in conjunction
with the annual Scientific Meeting (see below). A Steering Committee Chair will
be elected by majority vote from among the U19 PD/PIs at the first Steering
Committee meeting.

The responsibilities of the CMCR Steering
Committee will be to:

Evaluate progress
of the U19 projects and provide guidance;

Establish protocols
for the review and modification of ongoing studies, which may include
modification of project Milestones and recommendations for new
collaborations and resource allocations among the program members;

Ensure the timely
release of data to NIH-supported and/or public databases; and

Determine and
coordinate the use of Cooperative Resources (see below) by the program
members, including reagents, samples, and services.

Promote synergistic
interactions among the Centers and with other relevant groups

Develop a policy on
publication and sharing of data obtained by the collaborative efforts of
the Centers.

NIAID intends to support the peer-reviewed
studies proposed in the awarded grant applications. However, under special
circumstances, the Steering Committee will establish guidelines and review
procedures to evaluate and determine opportunities for redirection or
modification of the peer-reviewed projects. This policy is in keeping with the
terms and conditions of the cooperative agreement mechanism.

Scientific Meetings

All awardees will participate together in an
initial meeting, arranged by the NIAID Project Scientist, to be held soon after
award in the Washington, DC area; and will participate in face-to-face
scientific meetings of all PDs/PIs to be held annually thereafter. Quarterly
teleconferences of the Steering Committee will also be held. All PDs/PIs are
required to attend these meetings, together with additional scientific staff
from their CMCR when appropriate. The scientific meetings are open to members
of the CMCR program, NIH extramural staff and members of U.S. Government
agencies, and will serve as opportunities for members to provide the latest
update on their research, exchange ideas and information, and discuss
collaborations among program members. Meeting participants will identify the
group’s tangible resources, capabilities, and needs to advance overall program
goals. The PDs/PIs are required to give oral presentations at the annual
meetings on current progress and planned activities and projects.

2.A.4. Dispute Resolution

Any disagreements that may arise in scientific or programmatic
matters (within the scope of the award) between award recipients and the NIH
may be brought to dispute resolution. A Dispute Resolution Panel composed of
three members will be convened: a designee of the Steering Committee chosen
without NIH staff voting, one NIH designee, and a third designee with expertise
in the relevant area who is chosen by the other two; in the case of individual
disagreement, the first member may be chosen by the individual awardee. This
special dispute resolution procedure in no way affects the awardee's right to
appeal an adverse action that is otherwise appealable in accordance with PHS
regulations 42 CFR Part 50, Subpart D and HHS regulations 45 CFR Part 16.

The annual progress report for the U19 award
will use the standard PHS 2590 form. In addition, an executive summary and a
detailed description of the work done to achieve the specific Milestones for
that funding year shall be included. If Milestones have not been met, an
explanation of what has been accomplished and the alternatives, solutions,
and/or problems that exist must be provided. If future year Milestones need to
be modified, updated Milestones and associated timelines must be included in
the report and reviewed with the Program Officer. The Program Officer, in
conjunction with the Steering Committee, will determine if major changes are
appropriate and provide approval. In addition, the awardees may be contacted
during or after the completion of this award for information helpful in
assessing the overall impact of the program.

A
final progress report, invention statement, and Financial Status Report are
required when an award is relinquished when a recipient changes institutions or
when an award is terminated.

Section VII. Agency Contacts

We encourage your inquiries concerning this
funding opportunity and welcome the opportunity to answer questions from
potential applicants. Inquiries may fall into three areas: scientific/research,
peer review, and financial or grants management issues:

Human Subjects Protection:Federal
regulations (45CFR46) require that applications and proposals involving human
subjects must be evaluated with reference to the risks to the subjects, the
adequacy of protection against these risks, the potential benefits of the
research to the subjects and others, and the importance of the knowledge gained
or to be gained (http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm).

Data and Safety Monitoring Plan:Data
and safety monitoring is required for all types of clinical trials, including
physiologic toxicity and dose-finding studies (phase I); efficacy studies
(Phase II); efficacy, effectiveness and comparative trials (Phase III).
Monitoring should be commensurate with risk. The establishment of data and
safety monitoring boards (DSMBs) is required for multi-site clinical trials
involving interventions that entail potential risks to the participants (NIH
Policy for Data and Safety Monitoring, NIH Guide for Grants and Contracts, http://grants.nih.gov/grants/guide/notice-files/not98-084.html).

Sharing Research Data:Investigators
submitting an NIH application seeking $500,000 or more in direct costs in any
single year are expected to include a plan for data sharing or state why this
is not possible (http://grants.nih.gov/grants/policy/data_sharing).

Investigators
should seek guidance from their institutions, on issues related to
institutional policies and local IRB rules, as well as local, State and Federal
laws and regulations, including the Privacy Rule. Reviewers will consider the
data sharing plan but will not factor the plan into the determination of the
scientific merit or the priority score.

Policy for Genome-Wide Association Studies (GWAS):NIH is interested in
advancing genome-wide association studies (GWAS) to identify common genetic
factors that influence health and disease through a centralized GWAS data
repository. For the purposes of this policy, a genome-wide association study is
defined as any study of genetic variation across the entire human genome that
is designed to identify genetic associations with observable traits (such as
blood pressure or weight), or the presence or absence of a disease or
condition. All applications, regardless of the amount requested, proposing a
genome-wide association study are expected to provide a plan for submission of
GWAS data to the NIH-designated GWAS data repository, or provide an appropriate
explanation why submission to the repository is not possible. Data repository
management (submission and access) is governed by the Policy for Sharing of
Data Obtained in NIH Supported or Conducted Genome-Wide Association Studies, NIH Guide NOT-OD-07-088.
For additional information, see http://grants.nih.gov/grants/gwas/.

Access to Research Data through the Freedom
of Information Act:The
Office of Management and Budget (OMB) Circular A-110 has been revised to
provide access to research data through the Freedom of Information Act (FOIA)
under some circumstances. Data that are (1) first produced in a project that is
supported in whole or in part with Federal funds and (2) cited publicly and
officially by a Federal agency in support of an action that has the force and
effect of law (i.e., a regulation) may be accessed through FOIA. It is
important for applicants to understand the basic scope of this amendment. NIH
has provided guidance at http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm.
Applicants may wish to place data collected under this funding opportunity in a
public archive, which can provide protections for the data and manage the
distribution for an indefinite period of time. If so, the application should
include a description of the archiving plan in the study design and include
information about this in the budget justification section of the application.
In addition, applicants should think about how to structure informed consent
statements and other human subjects procedures given the potential for wider
use of data collected under this award.

Sharing of Model Organisms:NIH
is committed to support efforts that encourage sharing of important research
resources including the sharing of model organisms for biomedical research (see http://grants.nih.gov/grants/policy/model_organism/index.htm).
At the same time the NIH recognizes the rights of grantees and contractors to
elect and retain title to subject inventions developed with Federal funding
pursuant to the Bayh Dole Act (see the NIH Grants Policy Statement http://grants.nih.gov/archive/archive/grants/policy/nihgps_2003/index.htm).
All investigators submitting an NIH application or contract proposal, beginning
with the October 1, 2004 receipt date, are expected to include in the
application/proposal a description of a specific plan for sharing and
distributing unique model organism research resources generated using NIH
funding or state why such sharing is restricted or not possible. This will
permit other researchers to benefit from the resources developed with public
funding. The inclusion of a model organism sharing plan is not subject to a
cost threshold in any year and is expected to be included in all applications
where the development of model organisms is anticipated.

Inclusion of Women And Minorities in Clinical Research:It
is the policy of the NIH that women and members of minority groups and their
sub-populations must be included in all NIH-supported clinical research
projects unless a clear and compelling justification is provided indicating
that inclusion is inappropriate with respect to the health of the subjects or
the purpose of the research. This policy results from the NIH Revitalization
Act of 1993 (Section 492B of Public Law 103-43). All investigators proposing
clinical research should read the "NIH Guidelines for Inclusion of Women
and Minorities as Subjects in Clinical Research (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html);
a complete copy of the updated Guidelines is available at http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm.
The amended policy incorporates: the use of an NIH definition of clinical
research; updated racial and ethnic categories in compliance with the new OMB
standards; clarification of language governing NIH-defined Phase III clinical
trials consistent with the new PHS Form 398; and updated roles and
responsibilities of NIH staff and the extramural community. The policy
continues to require for all NIH-defined Phase III clinical trials that: a) all
applications or proposals and/or protocols must provide a description of plans to
conduct analyses, as appropriate, to address differences by sex/gender and/or
racial/ethnic groups, including subgroups if applicable; and b) investigators
must report annual accrual and progress in conducting analyses, as appropriate,
by sex/gender and/or racial/ethnic group differences.

Inclusion of Children as Participants in Clinical
Research:The
NIH maintains a policy that children (i.e., individuals under the age of 21)
must be included in all clinical research, conducted or supported by the NIH,
unless there are scientific and ethical reasons not to include them.

Required Education on the Protection of Human Subject
Participants:NIH
policy requires education on the protection of human subject participants for
all investigators submitting NIH applications for research involving human
subjects and individuals designated as key personnel. The policy is available
at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.

NIH Public Access Policy Requirement:In accordance with the NIH Public Access Policy (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-08-033.html) investigators must submit or have submitted for them
their final, peer-reviewed manuscripts that arise from NIH funds and are
accepted for publication as of April 7, 2008 to PubMed Central (http://www.pubmedcentral.nih.gov/),
to be made publicly available no later than 12 months after publication. As of
May 27, 2008, investigators must include the PubMed Central reference number
when citing an article in NIH applications, proposals, and progress reports
that fall under the policy, and was authored or co-authored by the investigator
or arose from the investigator’s NIH award. For more information,
see the Public Access webpage at http://publicaccess.nih.gov/.

Standards for Privacy of Individually
Identifiable Health Information:The
Department of Health and Human Services (DHHS) issued final modification to the
"Standards for Privacy of Individually Identifiable Health
Information", the "Privacy Rule", on August 14, 2002. The
Privacy Rule is a federal regulation under the Health Insurance Portability and
Accountability Act (HIPAA) of 1996 that governs the protection of individually
identifiable health information, and is administered and enforced by the DHHS
Office for Civil Rights (OCR).

Decisions
about applicability and implementation of the Privacy Rule reside with the
researcher and his/her institution. The OCR website (http://www.hhs.gov/ocr/) provides
information on the Privacy Rule, including a complete Regulation Text and a set
of decision tools on "Am I a covered entity?" Information on the
impact of the HIPAA Privacy Rule on NIH processes involving the review,
funding, and progress monitoring of grants, cooperative agreements, and
research contracts can be found at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-025.html.

URLs in NIH Grant Applications or Appendices:
All applications and proposals for NIH funding must be self-contained within
specified page limitations. For publications listed in the appendix and/or Progress
report, internet addresses (URLs) must be used for publicly accessible on-line journal articles. Unless otherwise specified in this solicitation, Internet addresses (URLs) should not be used to provide
any other information necessary for the review because reviewers are
under no obligation to view the Internet sites. Furthermore, we caution
reviewers that their anonymity may be compromised when they directly access an
Internet site.

Healthy People 2010:The
Public Health Service (PHS) is committed to achieving the health promotion and
disease prevention objectives of "Healthy People 2010," a PHS-led
national activity for setting priority areas. This FOA is related to one or
more of the priority areas. Potential applicants may obtain a copy of "Healthy
People 2010" at http://www.health.gov/healthypeople.

Authority and Regulations:This program is described in the Catalog of Federal
Domestic Assistance at http://www.cfda.gov/ and is not subject to the intergovernmental review requirements
of Executive Order 12372. Awards are made under the authorization of Sections
301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284)
and under Federal Regulations 42 CFR 52 and 45 CFR Parts 74 and 92. All awards
are subject to the terms and conditions, cost principles, and other
considerations described in the NIH Grants Policy Statement. The
NIH Grants Policy Statement can be found at http://grants.nih.gov/grants/policy/policy.htm.

The
PHS strongly encourages all grant recipients to provide a smoke-free workplace
and discourage the use of all tobacco products. In addition, Public Law 103-227,
the Pro-Children Act of 1994, prohibits smoking in certain facilities (or in
some cases, any portion of a facility) in which regular or routine education,
library, day care, health care, or early childhood development services are
provided to children. This is consistent with the PHS mission to protect and
advance the physical and mental health of the American people.

Loan Repayment Programs:NIH
encourages applications for educational loan repayment from qualified health
professionals who have made a commitment to pursue a research career involving
clinical, pediatric, contraception, infertility, and health disparities related
areas. The LRP is an important component of NIH's efforts to recruit and retain
the next generation of researchers by providing the means for developing a
research career unfettered by the burden of student loan debt. Note that an NIH
grant is not required for eligibility and concurrent career award and LRP
applications are encouraged. The periods of career award and LRP award may
overlap providing the LRP recipient with the required commitment of time and
effort, as LRP awardees must commit at least 50% of their time (at least 20
hours per week based on a 40 hour week) for two years to the research. For
further information, please see: http://www.lrp.nih.gov.